Study of VX-809 Alone and in Combination With VX-770 in Cystic Fibrosis (CF) Patients Homozygous or Heterozygous for the F508del-CFTR Mutation

Cystic Fibrosis Clinical Trial

Official title:

A Phase 2, Multicenter, Double-Blinded, Placebo-Controlled, Multiple-Dose Study to Evaluate Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of Lumacaftor Monotherapy, and Lumacaftor and Ivacaftor Combination Therapy in Subjects With Cystic Fibrosis, Homozygous or Heterozygous for the F508del-CFTR Mutation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01225211
• Other study ID #: VX09-809-102
• Secondary ID: 2010-020413-90
• Status: Completed
• Phase: Phase 2
• First received: October 15, 2010
• Last updated: September 2, 2015
• Start date: October 2010
• Est. completion date: April 2014

Study information

• Verified date: September 2015
• Source: Vertex Pharmaceuticals Incorporated
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationAustralia: Therapeutic Goods AdministrationBelgium: Federal Agency for Medicinal Products and Health ProductsGermany: Federal Institute for Drugs and Medical DevicesNew Zealand: MedsafeUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyIreland: Ministry of HealthFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate of the safety, efficacy, pharmacokinetics (PK) and pharmacodynamic (PD) effects of lumacaftor (VX-809) alone and when coadministered with ivacaftor (VX-770) in participants with cystic fibrosis, homozygous or heterozygous for the F508del-CFTR mutation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 312
• Est. completion date: April 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or female participants with confirmed diagnosis of CF

• Must have the F508del-CFTR mutation on at least 1 allele.

• FEV1 greater than equal (>=) 40% of predicted normal for age, gender, and height (Knudson standards)(Cohort 1, 2, and 3); FEV1 40-90% of predicted normal for age, gender, and height (Hankinson standards (Cohort 4)

• Participant of child-bearing potential and who are sexually active must meet the contraception requirements

Exclusion Criteria:

• History of any illness or condition that, in the opinion of the investigator might confound the results of the study or pose an additional risk in administering study drug to the participant (e.g., cirrhosis with portal hypertension).

• An acute illness including acute upper or lower respiratory infection, pulmonary exacerbation or changes in therapy (including antibiotics) for pulmonary disease within 14 days (Cohort 1, 2, and 3) or 28 days (Cohort 4) before receiving the first dose of study drug.

• History of solid organ or hematological transplantation.

• History of alcohol abuse or drug addiction in the past year, including cannabis, cocaine, and opiates.

• Ongoing participation in another therapeutic clinical study, or prior participation in an investigational drug study without appropriate washout

• Pregnant or nursing females; females of childbearing potential who are unwilling or unable to use an acceptable method of non-hormonal contraception

• Participants enrolled in Cohort 1 or Cohort 2 will not be eligible for Cohort 3

• Ongoing or prior participation in an investigational drug study within 30 days of the Screening Visit

• Heterozygous participants who participated in Cohort 2 and meet the eligibility criteria for Cohort 4 may participate in Cohort 4

• Evidence of lens opacity or cataract as determined by the ophthalmologic examination (Cohort 4 only)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• Lumacaftor
Tablet
• Ivacaftor
Tablet.
• Lumacaftor Placebo
Matching placebo tablet.
• Ivacaftor Placebo
Matching placebo tablet.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Vertex Pharmaceuticals Incorporated

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  France,  Germany,  New Zealand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cohort 1: Safety and Tolerability Based on Adverse Events (AEs)	AE: any untoward medical occurrence in a participant during study; irrespective of relationship with treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after informed consent. AE includes serious AEs (SAEs) as well as Non-SAEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Number of participants with AEs and SAEs are reported. AE that started at/after initial dosing of study drug, or increased in severity after initial dosing of study drug is considered treatment-emergent. Results are reported separately for monotherapy period (Period 1: Day 1 to Day 14) and combination therapy period (Period 2: Day 15 to Day 21).	Cohort 1: Day 1 up to 28 days after last dose (Last dose = Day 21)	Yes
Primary	Cohort 2 and 3: Safety and Tolerability Based on Adverse Events (AEs)	Detailed description is provided in Outcome Measure 1. Results are reported separately for monotherapy period (Period 1: Day 1 to Day 28) and combination therapy period (Period 2: Day 29 to Day 56).	Cohort 2 and 3: Day 1 up to 28 days after last dose (Last dose = Day 56)	Yes
Primary	Cohort 4: Safety and Tolerability Assessed by Number of Participants With AEs and SAEs	AEs and SAEs are defined in Outcome Measure 1.	Cohort 4: Day 1 up to 28 days after last dose (Last dose = Day 56)	Yes
Primary	Cohort 1: Absolute Change From Day 14 in Sweat Chloride at Day 21		Cohort 1: Day 14, Day 21	No
Primary	Cohort 2 And 3: Absolute Change From Day 28 in Sweat Chloride at Day 56		Cohort 2 and 3: Day 28, Day 56	No
Primary	Cohort 4: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 56	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. ppFEV1 (predicted for age, gender, and height) was calculated using the Hankinson method.	Cohort 4: Baseline, Day 56	No
Secondary	Cohort 1: Absolute Change From Baseline in Sweat Chloride at Day 14		Cohort 1: Baseline, Day 14	No
Secondary	Cohort 2 And 3: Absolute Change From Baseline in Sweat Chloride at Day 14		Cohort 2: Baseline, Day 14	No
Secondary	Cohort 4: Absolute Change From Baseline in Sweat Chloride at Day 56		Cohort 4: Baseline, Day 56	No
Secondary	Cohort 1: Absolute Change From Day 14 in FEV1 at Day 21	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.	Cohort 1: Day 14, Day 21	No
Secondary	Cohort 1: Absolute Change From Day 14 in ppFEV1 at Day 21	FEV1 and ppFEV1 are defined in Outcome Measure 6.	Cohort 1: Day 14, Day 21	No
Secondary	Cohort 2 and 3: Absolute Change From Day 28 in ppFEV1 at Day 56	FEV1 and ppFEV1 are defined in Outcome Measure 6.	Cohort 2 and 3: Day 28, Day 56	No
Secondary	Cohort 2 and 3: Relative Change From Day 28 in ppFEV1 at Day 56	FEV1 and ppFEV1 are defined in Outcome Measure 6.	Cohort 2 and 3: Day 28, Day 56	No
Secondary	Cohort 2 and 3: Absolute Change From Baseline in ppFEV1 at Day 28 and 56	FEV1 and ppFEV1 are defined in Outcome Measure 6.	Cohort 2 and 3: Baseline, Day 28 and 56	No
Secondary	Cohort 2 and 3: Relative Change From Baseline in FEV1 at Day 28 and 56	FEV1 and ppFEV1 are defined in Outcome Measure 6.	Cohort 2 and 3: Baseline, Day 28 and 56	No
Secondary	Cohort 4: Relative Change From Baseline in Percent Predicted FEV1 at Day 56	FEV1 and ppFEV1 are defined in Outcome Measure 6.	Cohort 4: Baseline, Day 56	No
Secondary	Cohort 2 and 3: Absolute Change From Day 28 in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Day 56	The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for subjects with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.	Cohort 2 and 3: Day 28, Day 56	No
Secondary	Cohort 4: Absolute Change From Baseline in CFQ-R Respiratory Domain Score at Day 56	CFQ-R respiratory domain is defined in Outcome Measure 17.	Cohort 4: Baseline, Day 56	No
Secondary	Cohort 4: Absolute Change From Baseline in Body Mass Index (BMI) at Day 56	BMI was defined as weight in kilogram (kg) divided by height*height in square meter (m^2).	Cohort 4: Baseline, Day 56	No
Secondary	Cohort 4: Absolute Change From Baseline in Weight at Day 56		Cohort 4: Baseline, Day 56	No